MX2013009976A - Enhanced bioavailable iodine molecules. - Google Patents

Abstract

This invention relates to supplementation of the diets of domesticated animals (livestock and poultry) with iodine in an enhanced bioavailable manner, that is to say the iodine is more available to the animal than when using conventional sources of iodine, such as calcium iodate. The supplementary compound are alpha amino acid metal iodide complexes.

Description

IMPROVED BIODY-AVAILABLE IODINE MOLECULES BACKGROUND OF THE INVENTION This invention relates to the supplementation of the diets of domesticated animals (livestock and poultry) with iodine in an improved bioavailable manner, ie the iodine is more available to the animal than when conventional sources of iodine are used, such as iodate of iodine. calcium. The supplemental compound are alpha amino acid iodide metal complexes.

It is well known that domesticated animals (livestock and poultry) are in need of bioavailable metal or mineral supplements, essential amino acids and are also in need of iodine for healthy animal nutrition.

Iodine is a key component of the hormones produced by the thyroid gland. The thyroid is responsible for the growth, development of the brain and the rate at which animals burn energy. Two of the most common sources of iodine used in animal nutrition and therefore used in supplementing animal diets are calcium iodate (CaI03) and ethylenediamine dihydroiodide (EDDI). A test of the efficiency of the effective metabolization of the iodine source by an animal is to measure the iodine levels in the blood serum after the intake of the nutrient material.

In the animal food industry it is known that insufficient availability of iodine to the animal can result in conditions such as goiters, reproductive failure, weak breed, reduced milk yield, mastitis, abnormal respiration, reduced growth rate and even hairless breeds. The symptoms of traditional iodine toxicity in animals are anorexia, excessive salivation, nasal or ocular discharge, abortion, pneumonia and bone / tendon deformities. In addition, excessive feeding of ethylenediamine dihydroiodide (EDDI) is known to interfere with the metabolism of Vitamin A. The high diet of calcium nitrate, thiocyanate, glucosinolate, perchlorate, rubidium and cobalt interferes with the metabolism of iodine and can increase the iodine requirements. Metal iron for nutrient use reduces the toxicity of iodine, but may also increase the need for iodine requirements.

Therefore, it can be seen that conventionally used iodine sources in animal feed, such as inorganic iodine salts or amine salts all have their unique problems. Therefore, there is a continuing need for the development of unique iodine sources that provide better availability to the animal, that is, higher blood serum levels without simply adding more iodine. The primary objective of the present invention is to meet this need by providing iodine organic minor mineral metal complexes, particularly with amino acid metal complexes, and much more particularly with naturally occurring amino acids and / or metal essential amino acid complexes.

Lysine is an essential amino acid in the diet of mammals. That is to say, lysine can not be synthesized by mammals at an adequate rate to meet metabolic requirements and therefore must be supplied in the diet. Corn is notoriously low in lysine, and if used for animals in a single grain ration, requires lysine supplementation both to maintain the animal's health and to achieve economic growth of the animal. Protected lysine molecules are a common property objective of U.S. Patent Nos. 7,704,521 and 7,846,471. As explained below, the preferred compounds of the present invention that provide enhanced bioavailability of iodine by providing two iodine ions per molecule and are those made from lysine reacted with a compound such as zinc to make zinc diiodide of lysine (structure I, right away).

The method for achieving the above primary objective as well as others will become apparent from the detailed description of the invention. It is understood that the invention is not limits by its primary objective and that other advantages of the invention such as efficiency of synthesis, lower cost of iodine, increase of iodine in the level of serum in the blood, that is, bioavailability and cost effectiveness of nutritional supplementation are also all achieved BRIEF DESCRIPTION OF THE INVENTION Metal amino acid iodide molecules, preferably metal lysine diiodides having a portion of iodine associated with the metal atom and the second associated with the amine salt are prepared and used to provide improved biodi-available iodine supplementation of animals (livestock and poultry) with resulting increased serum iodine levels in the blood.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES In the ruminant animal, the ingested food first passes into the rumen where it is partially broken down by bacterial fermentation. During the rumen fermentation, the rumen microbes use nitrogen from the nitrogen compounds that have degraded to form microbial protein. Nitrogen sources for rumen microbes include degradable protein; rumen and peptides, free amino acids and urea. The microbial protein and the non-degraded food protein go to the abomasum and the small intestine where the hydrochloric acid and the mammalian enzymes degrade the microbial protein and the protein of food not degraded to free amino acids and short peptides. Amino acids and short peptides are absorbed in the intestine and ruminant animals use amino acids for the synthesis of protein to sustain life, growth, reproduce and produce milk.

Of the twenty or more amino acids used by the animal to synthesize proteins, nine are considered essential. Examples of the essential amino acids include leucine, isoleucine, valine, methionine, threonine, lysine, histidine, phenylalanine and tryptophan. The essential amino acids are those amino acids that are required in quantities that exceed amounts produced by the animal, and must be supplied by microbial protein or non-degraded rumen protein. The amino acids supplied in excess are degraded by the animal and excreted in the form of urea. The process to synthesize the ammonia urea is a process that requires input of energy from the animal. If certain essential amino acids are not proposed in adequate amounts, the animal will be limited in the; amount and type of protein that can produce, in this way limiting the performance of the animal. Therefore, providing the appropriate amounts of essential amino acids maximizes the performance of the animal while increasing the efficiency of energy utilization by the animal.

Lysine and methionine are two of the amino acids much more limiting essentials when feeding corn-based rations. The results of studies also indicate that the protein content of milk is the most sensitive of the production variables (milk yield, fat-corrected milk, milk protein, milk fat and fat content and milk protein) to alterations in the amino acid content of duodenal digesta. Researchers have determined, by incremental amounts of infusion of the limiting amino acids in the duodenum of lactating dairy cows, that the required contribution of lysine and methionine to the total essential amino acids in the duodenal digesta for maximum milk protein content approached 15 % and 5.2%, respectively.

The present invention relates to certain iodine complexes that provide animal (livestock or poultry) supplementation that provides both the opportunity for essential amino acid supplementation, iodine supplementation and also provides a minor mineral. For the present knowledge of the Applicant, there have been no compounds that have provided, in the past, all of these supplements in the same compound. This is important because often space in a mixture of animal feed is sometimes a problem; and this invention meets three nutritional requirements with a molecule, with a pure result of improved bioavailability of iodine in blood serum compared to normal sources of iodine, such as EDDI and calcium iodine.

The much more preferred amino acid for use in the present invention is lysine to provide compounds such as zinc lysine diiodide of the formula: '(Structure I) As can be seen from Structure I, iodine is provided in this compound in two sources; first, in association with the zinc atom and second in the amine salt form of iodine. In this way there is an opportunity for "double improvement" with this compound. In other words, the structure has both an iodine salt iodine and a iodine metal salt. Structure I for lysine diiodides can be generalized by replacing the zinc atom that represents the metal ion. For the present invention, the suitable metal ions can be manganese and iron in case the generalized formula would be: (Generalized formula for metal diiodide lysine salts - Structure II) As mentioned hitherto, lysine is the preferred amino acid but not only the only one that can be employed in the present invention. M can be zinc, manganese or iron. In fact, the invention can be generalized to other naturally occurring amino acids as follows: In Structure III in the above formula, M represents the metal ion and can be zinc, manganese or iron. R represents any remaining portion of a naturally occurring amino acid and can be selected from the group derived from essential amino acids including leucine, isoleucine, valine, methionine, threonine, lysine, histidine, phenylalanine and tryptophan. The amino acid can also be one of the other 20 or more amino acids used by animals to synthesize proteins and also be a mixture of a variety of amino acids that lead to a mixture of iodine metal salts of amino acids (see Example II below).

It should be noted that in Structure (III) the amino group can be replaced with a hydroxy to form metal complexes of hydroxyl acid with iodine. Put another way to generalize, the amino group of Structure (III) can be replaced with "X", and "X" can be either amino or hydroxyl. Other possibilities include R is CH3, R is H, R is C2Hs and R is C2H4SCH3, in which case the acid is respectively lactic acid, glycolic acid, hydroxybutyric acid and hydroxy-methylthio-butyric acid (see Example III).

The process for preparing the amino acid metal iodine salts is direct, simply by mixing amounts in an aqueous medium of the amino acid and the source of the metal ion, for example if it is zinc, zinc iodide. It is stirred and heated for a sufficient time to allow the reaction to occur, preferably around 100 ° C for 30-40 minutes. This is followed by cooling to room temperature, drying to leave a solid which, if it is not in powder form, is milled to produce a powder. It can be dried by spraying or drying by rotary evaporation, etc. One of the efficiencies that provides cost effectiveness is the simple methodology for preparation.

The compounds prepared as in the above, and especially those listed as preferred, are easily processable. They can be sold as a supplemental additive or can be mixed with carriers to improve packaging, processability and taste. Preferred carriers are, for example, powdered sugar which significantly improves the taste for ruminants that they ingest the same. For example, the Benzaldehyde derivatives have an almond flavor which can be masked with powdered sugar.

The compounds can also be used as a part of the total minor mineral supplementation for the animal.

While it is preferred that the compounds of the present invention be added without additional carriers or filler material, as mentioned so far, flavorings can be used as or 1 with the carrier. If carriers are employed, the carrier may be suitable carriers such as soluble fermentation distillers, food grains, corn cob meal, whey or other cellulose carrier materials. They can also be added at the same time or with other minor mineral preparations.

The amount of supplement added to the feed ration will vary, of course, depending on whether the pure compositions or the composition are used with a carrier. Basically the supplement will simply be mixed with the food ration, as it is sold.

Generally the compounds must be added at a level to provide sufficient iodine essential for the performance levels of the animals and daily nutritional needs, that is, within the range of approximately 25 mg / head / day to approximately 50 milligrams per animal per day for the performance level and 5-10 mg / day for the nutrition level. In this way, the total range of addition is 5mg to 50mg per head per day, depending on the objective.

The following examples are offered to further illustrate but not to limit the compounds of the invention and how to show their use for the effective improvement of iodine supplementation in cattle or poultry at the level of serum in the blood.

EXAMPLE I Synthesis of Zinc Lysine Diiodide (Structure I) Lysine (4.24 g, 0.029 mole) was dissolved in water (200 mL). To this solution was added Znl2 (9.26 gr, 0.29 mol). This mixture was stirred and heated at 100 ° C for 35 minutes. This solution was allowed to cool to room temperature and the resulting solution was dried by rotary evaporation resulting in an off-white solid. The material was analyzed for zinc content and iodine content. The percentage of zinc 12.8 and percentage of Iodine 50.5.

EXAMPLE II Synthesis of Zinc iodide (Amino Acid) (Structure III with mixed amino acids and M = Z) A mixture of amino acids was prepared by mixing the following amino acids: This mixture of amino acids has an average molecular weight of 130.57 10. 2 g of this amino acid mixture (0.078 mol) was dispersed in 250 mL of water and Znl2 (24.9 g, 0.078 mol) was added. This mixture was heated until it was a solution. This solution then heated up! at 100 ° C for 28 minutes. The mixture was cooled to room temperature and the water was stirred by. rotary evaporation. The resulting product had 13.9 percent zinc and 53.2 percent iodine.

EXAMPLE III (Zinc hydroxy-methylthio-bütiric acid iodide) (Structure III, M = Z and R is methionine) Hydroxyl methylthio butanoic acid (88% solution) (35.7 g, 0.21 mol) was dissolved in 350 mL of water. TO this mixture was added Z.nl2 (67 g, 0.21 mol). This mixture was stirred and the pH was adjusted to pH = 3 by the addition of ION NaOH dropwise. The mixture was heated for 1.5 hours at 100 ° C. The resulting mixture was cooled and then dried to a solid by rotary evaporation. This solid was analyzed for 11.9% zinc and 30% iodine.

EXAMPLE IV (Zinc glycine iodide) (Structure III, M = Zn and glycine) Glycine (28.6 g, 0.381 mol) was dissolved in 150 mL of water. Znl2 (121.6 g, 0.381 mol) was added to this mixture and the whole solution was stirred and heated at 100 ° C for 45 minutes. The mixture was cooled to room temperature and the solvent was removed by rotary evaporation. The solid is analyzed for zinc and iodine. The dried product is analyzed for 14.3% zinc and 40% iodine.

EXAMPLE V (Synthesis of Iron Lysine Diiodide) Lysine (4.76 g, 0.0326 mol) was dissolved in water (100 mL). To this solution was added FeI2 (10.1 gr, 0.0326 moles). This mixture was stirred and heated at 100 ° C for 35 minutes. This solution was allowed to cool to room temperature and the resulting solution was dried by rotary evaporation resulting in a brown solid. He material was analyzed for iron content and iodine content. Iron percentage 11.7% and percentage of Iodine 53.4%.

EXAMPLE VI (Synthesis of Manganese Lysine Diiodide) Lysine was dissolved (4.7 g, (L0323 mol) in water (lOOmL). To this solution was added Mnl2 (10.1 gr, 0.0323 mol). This mixture was stirred and heated at 100 ° C for 35 minutes. This solution was allowed to cool to room temperature and the resulting solution was dried by rotary evaporation resulting in an off-white solid. The material was analyzed for zinc content and iodine content. Manganese percentage 11.6% and percentage of Iodine 52.1%.

EXAMPLE VII This example illustrates improved levels of iodine in blood serum, which demonstrate superiority over conventional sources.

EDDI = ethylenediamine dihydroiodide CaI03 = Calcium Yodate Pregnant, non-lactating beef cows, Angus Simmental, weighing between 1200 and 1700 lbs were assigned to a study with a "completely randomized block design to determine the effect of novel iodine compounds on the concentration of iodine in serum as compared to EDDI and CaI03. The cows were blocked in body weight in 7 days before the start of the test. The cows were fed with a bolus containing 60 mg of iodine from the various sources from day 0 to day 10. The serum iodine in the blood was measured and reported as an average of day 2-14 and as a peak value on day 10. Compounds 1 and 2 showed higher levels of iodine in the blood than CaI03 or EDDI. 60 mg of Iodine / day for 10 days EXAMPLE VI I I another efficacy test, pregnant, non-lactating, Angus Simmental beef cows, weighing between 1200 and 1700 lbs were assigned to a study with a completely randomized block design to determine the effect of novel iodine compounds as compared with EDDI and CaI03 in serum iodine concentration. The cows were blocked in body weight 7 days before the start of the test. 60 mg of Iodine / day for 10 days As can be seen from the above examples, the iodine bound to the metal amino acid is producing a much higher iodine blood serum level than the standard materials (EDDI, CaI03), which indicate improved bioavailable iodine levels.

Similar results are achieved if the metal is manganese or iron, and if other naturally occurring amino acids are used, individually or in combination.

Claims (1)

1. CLAIMS 1. A method for improving the bioavailability of iodine in livestock and poultry from iodine nutrient sources, characterized in that it comprises: Feed animals with an effective amount of nutritional supplementation of an essential metal amino acid iodide of the formula: wherein M is a metal ion selected from the group consisting of zinc, manganese and iron, and R is a portion selected to provide the backbone of a naturally occurring amino acid to an animal in need of iodine supplementation. 2. The method according to claim 1, characterized in that the effective amount of diet supplementation is an amount sufficient to provide a level of about 5 milligrams per head per day to about 50 milligrams of iodine per head per day. 3. The method according to claim 1, characterized in that the supplement is added in conjunction with non-toxic carriers. 4. The method in accordance with the claim 3, characterized in that the non-toxic carriers are selected from the group consisting of sugars, soluble fermentation materials, food grains, corn cob meal, whey and other cellulose carrier materials. 5. The method according to claim 1, characterized in that the amino acid is an essential amino acid selected from the group consisting of leucine, isoleucine, valine, methionine, threonine, lysine, histidine, phenylalanine and tryptophan. 6. A method for improving the bioavailability of iodine in livestock and poultry from iodine nutrient sources, characterized in that it comprises: Feed animals with an effective amount of nutritional supplementation of a metal lysine diiodide of the formula: wherein M is a metal ion selected from the group consisting of zinc, manganese and iron. 7. The method according to claim 6, characterized in that the effective amount of diet supplementation is an amount sufficient to provide a level of approximately 5 milligrams per head per day to approximately 50 milligrams of iodine per head per day. 8. The method according to claim 6, characterized in that the supplement is added in conjunction with non-toxic carriers. 9. The method according to claim 8, characterized in that the non-toxic carriers are selected from the group consisting of sugars, soluble fermentation materials, food grains, corn cob meal, whey and other carrier materials. of lysine diiodide characterized in that it is a metal ion selected from the group consisting of zinc, manganese and iron. 11. The compound according to claim 10, characterized in that M is zinc. 12. The compound according to claim 10, characterized in that M is manganese. 13. The compound according to claim 10, characterized in that M is iron. 14. Acid hydroxyl metal complexes with iodine of the formula: characterized in that M is a metal selected from the group consisting of zinc, manganese and iron, and R is selected from the group consisting of hydrogen, methyl, ethyl and 2- (methylthio) ethyl. 15. The metal complex according to claim 14, characterized in that R is 2- (methylthio) -ethyl. 16. A method for improving the bioavailability of iodine in livestock and poultry, characterized in that it comprises: Feed animals with an effective amount of nutritional supplementation of hydroxyl metal complex with iodine of the formula: where M is a metal selected from the group consisting of zinc, manganese and iron, and R is selected from the group consisting of hydrogen, methyl, ethyl and 2- (methylthio) ethyl. 17. The method according to claim 16, characterized in that the effective amount of diet supplementation is an amount sufficient to provide a level of approximately 5 milligrams per head per day to approximately 50 milligrams of iodine per head per day. 18. The method according to claim 16, characterized in that the supplement is added in conjunction with non-toxic carriers. 19. The method according to claim 18, characterized in that the non-toxic carriers are selected from the group consisting of sugars, soluble fermentation materials, food grains, corn cob meal, whey and other cellulose carrier materials.